The .alpha.-naphthyl-propionic acids are known from the literature for their biological properties. Owing to the presence of the asymmetric carbon atom bearing the naphthyl moiety, they can exist both as racemic mixtures and in the form of the corresponding d or l optically active isomers.
Of particular interest for its excellent antiphlogistic activity is the d isomer of the compounds of formula I, in which R.sub.1 represents methyl and R.sub.2 stands for hydrogen, namely the d-2-(6-methoxy-2-naphthyl)-propionic acid.
It was first described in U.S. Pat. No. 3,904,682 and is internationally known as naproxen.
Several methods for its preparation are reported in the art literature, including the patent literature. Typically, these methods contemplate the synthesis of d,l-2-(6-methoxy-2-naphthyl)-propionic acid, or a precursor thereof, and the subsequent resolution into the optical antipodes via formation of salts with optically active organic bases like cinchonidine, dehydroabietylamine, N-methyl-D-glucamine or, in general, N-alkyl-D-glucamins (see, for instance, French Publication No. 2,035,846 and U.S. Pat. Nos. 3,683,015; 4,246,164; 4,246,193 and 4,423,244). All of these resolution methods possess more or less severe drawbacks. As an example, it is often necessary to carry out several recrystallizations for obtaining the salt of the desired isomer in a pure form. In addition, their workability is considerably influenced by the purity degree of the material to be resolved.
Attempts for avoiding these drawbacks have led to stereospecific synthesis of naproxen and, in general, optically active .alpha.-naphthyl-propionic acids (see European laid open applications Nos. 81993 and 110671). To our experience, however, these procedures appear to involve a lot of problems, like the use of Grignard's reagents and the possibility of inversion of configuration.
Therefore, in the preparation of optically active .alpha.-naphthyl-propionic acids, there is still the need of valuable and economical resolution methods.